Please use this identifier to cite or link to this item:
https://doi.org/10.1371/journal.pone.0006104
DC Field | Value | |
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dc.title | Absence of leucine zipper in the natural FOXP3Delta2Delta7 isoform does not affect dimerization but abrogates suppressive capacity | |
dc.contributor.author | Mailer R.K.W. | |
dc.contributor.author | Falk K. | |
dc.contributor.author | Rötzschke O. | |
dc.date.accessioned | 2020-03-18T05:52:05Z | |
dc.date.available | 2020-03-18T05:52:05Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | Mailer R.K.W., Falk K., Rötzschke O. (2009). Absence of leucine zipper in the natural FOXP3Delta2Delta7 isoform does not affect dimerization but abrogates suppressive capacity. PLoS ONE 4 (7) : e6104. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0006104 | |
dc.identifier.issn | 19326203 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/165604 | |
dc.description.abstract | Background: Phenotype and function of regulatory T cells (Treg) largely depend on the presence of the transcription factor FOXP3. In contrast to mice, human Treg cells express isoforms of this protein. Besides the full length version (FOXP3fl), an isoform lacking the exon 2 (FOXP3Delta2) is co-expressed in comparable amounts. Recently, a third splice variant has been described that in addition to exon 2 also misses exon 7 (FOXP3Delta2Delta7). Exon 7 encodes for a leucine zipper motif commonly used as structural dimerization element. Mutations in exon 7 have been linked to IPEX, a severe autoimmune disease suggested to be caused by impaired dimerization of the FOXP3 protein. Principal Findings: This study shows that the lack of exon 7 does not affect (homo-) dimerization. Moreover, the interaction of FOXP3Delta2Delta7 to RUNX1, NFAT and NF-kB appeared to be unchanged in co-immunoprecipitation experiments and reporter gene assays, when compared to FOXP3fl and FOXP3Delta2. Nevertheless, retroviral transduction with FOXP3Delta2Delta7 failed to induce the typical Treg-associated phenotype. The expression of FOXP3-induced surface molecules such as CD25 and CTLA4 were not enhanced in FOXP3D2D7 transduced CD4+ T cells, which also failed to exhibit any suppressive capacity. Notably, however, co-expression of FOXP3fl with FOXP3Delta2Delta7 resulted in a reduction of CD25 expression by a dominant negative effect. Conclusions: The leucine zipper of FOXP3 does not mediate dimerization or interaction with NFAT, NF-kB and RUNX1, but is indispensable for the characteristic phenotype and function in Treg cells. FOXP3Delta2Delta7 could play a role in regulating the function of the other FOXP3 isoforms and may be involved in cancer pathogenesis, as it is overexpressed by certain malignant cells. © 2009 Mailer et al. | |
dc.publisher | Public Library of Science | |
dc.source | Unpaywall 20200320 | |
dc.subject | cytotoxic T lymphocyte antigen 4 | |
dc.subject | immunoglobulin enhancer binding protein | |
dc.subject | interleukin 2 receptor alpha | |
dc.subject | isoprotein | |
dc.subject | leucine zipper protein | |
dc.subject | transcription factor FOXP3 | |
dc.subject | transcription factor NFAT | |
dc.subject | transcription factor RUNX1 | |
dc.subject | forkhead transcription factor | |
dc.subject | FOXP3 protein, human | |
dc.subject | immunoglobulin enhancer binding protein | |
dc.subject | isoprotein | |
dc.subject | leucine zipper protein | |
dc.subject | primer DNA | |
dc.subject | RUNX1 protein, human | |
dc.subject | transcription factor NFAT | |
dc.subject | transcription factor RUNX1 | |
dc.subject | animal cell | |
dc.subject | animal experiment | |
dc.subject | article | |
dc.subject | cancer cell | |
dc.subject | carcinogenesis | |
dc.subject | CD4+ T lymphocyte | |
dc.subject | cell function | |
dc.subject | controlled study | |
dc.subject | dimerization | |
dc.subject | exon | |
dc.subject | gene mutation | |
dc.subject | gene repression | |
dc.subject | gene transfer | |
dc.subject | genetic transcription | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | immunoprecipitation | |
dc.subject | IPEX syndrome | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | phenotype | |
dc.subject | protein binding | |
dc.subject | protein expression | |
dc.subject | protein function | |
dc.subject | protein interaction | |
dc.subject | protein localization | |
dc.subject | regulatory T lymphocyte | |
dc.subject | reporter gene | |
dc.subject | Retrovirus | |
dc.subject | animal | |
dc.subject | Bagg albino mouse | |
dc.subject | cell fractionation | |
dc.subject | chemistry | |
dc.subject | genetics | |
dc.subject | immunology | |
dc.subject | metabolism | |
dc.subject | nucleotide sequence | |
dc.subject | physiology | |
dc.subject | reverse transcription polymerase chain reaction | |
dc.subject | Mus | |
dc.subject | Animals | |
dc.subject | Base Sequence | |
dc.subject | Core Binding Factor Alpha 2 Subunit | |
dc.subject | Dimerization | |
dc.subject | DNA Primers | |
dc.subject | Exons | |
dc.subject | Forkhead Transcription Factors | |
dc.subject | Humans | |
dc.subject | Leucine Zippers | |
dc.subject | Mice | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | NF-kappa B | |
dc.subject | NFATC Transcription Factors | |
dc.subject | Protein Binding | |
dc.subject | Protein Isoforms | |
dc.subject | Reverse Transcriptase Polymerase Chain Reaction | |
dc.subject | Subcellular Fractions | |
dc.subject | T-Lymphocytes, Regulatory | |
dc.subject | Transcription, Genetic | |
dc.type | Article | |
dc.contributor.department | MICROBIOLOGY AND IMMUNOLOGY | |
dc.description.doi | 10.1371/journal.pone.0006104 | |
dc.description.sourcetitle | PLoS ONE | |
dc.description.volume | 4 | |
dc.description.issue | 7 | |
dc.description.page | e6104 | |
dc.published.state | Published | |
Appears in Collections: | Elements Staff Publications |
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